Population Balance Model-Based Multiobjective Optimization of a Multisegment Multiaddition (MSMA) Continuous Plug-Flow Antisolvent Crystallizer
Population Balance Model-Based Multiobjective Optimization of a Multisegment Multiaddition (MSMA) Continuous Plug-Flow Antisolvent Crystallizer
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基于群体平衡模型的多段多次添加 (MSMA) 连续推流式反溶剂结晶器的多目标优化
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发表时间：
2014
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通讯作者：
Z. Nagy
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作者：
Bradley J. Ridder;Aniruddha Majumder;Z. Nagy
结晶是制药工业中一个主要的分离过程。大多数结晶是分批进行的，但有很大的动机将其转化为连续操作。本文研究了一种特殊的抗溶剂塞流结晶器：多段多加成塞流结晶器（MSMA-PFC）的建模、仿真和优化。MSMA-PFC接受沿其长度的多种抗溶剂流动，允许更精细的过饱和控制。采用稳态种群平衡方程跟踪晶体尺寸分布，采用质量平衡方程跟踪溶解溶质（氟芬那酸）的耗竭。采用多目标优化框架确定各段的抗溶剂流量，同时使平均晶粒尺寸最大化，变异系数最小。根据不同的情况，用矩量法（MO）或矩量法（MO）来求解这组耦合微分方程。
Crystallization is a major separation process in the pharmaceutical industry. Most crystallizations are performed batchwise, but there is great incentive for converting them to continuous operations. This paper investigates the modeling, simulation, and optimization of a special antisolvent plug-flow crystallizer: the multisegmented, multiaddition plug-flow crystallizer (MSMA-PFC). The MSMA-PFC accepts multiple antisolvent flows along its length, permitting finer control of supersaturation. A steady-state population balance equation was applied for tracking the crystal size distribution, and a mass balance equation was used to track the depletion of dissolved solute (flufenamic acid). A multiobjective optimization framework was applied to determine the antisolvent flow rates into each segment that simultaneously maximize the average crystal size, and minimize the coefficient of variation. The set of coupled differential equations was solved, depending on circumstance, with either the method-of-moments (MO...